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Abstract
Aims Current understanding of oral squamous cell carcinoma (OSCC) is incomplete with regard to prognostic factors that lead to the considerable heterogeneity in treatment response and patient outcomes. We aimed to evaluate the impact of individual tumour-infiltrating lymphocyte (TIL) subsets on prognosis as a possible rationale for this, in a retrospective observational study.
Methods Immunohistochemistry was performed to quantitatively assess cell densities of CD3+, CD20+, CD4+, CD8+ and FOXP3+TIL subsets in 50 surgically treated OSCC cases. Results were correlated with disease-free survival (DFS) and overall survival (OS). Receiver operating characteristic curve analysis and Youden index were applied to determine prognostically significant cut-off values.
Results Mean counts for CD3+, CD4+, CD8+, CD20+ and FOXP3+TILs were 243, 52, 132, 53 and 116 cells per high power field, respectively. High CD8+ and low FOXP3+TIL counts, and high ratio of CD8:FOXP3 were significantly associated with longer DFS and OS, as well as with improved tumour–host interface parameters.
Conclusions Host immune response and its interaction with cancer cells have a significant impact on OSCC outcomes, with some TIL subsets being more clinically relevant than others. High cytotoxic T-cell (CD8) and low Treg (FOXP3) counts, and high cytotoxic T-cell to Treg (CD8:FOXP3) ratio are significantly associated with favourable prognosis. These results may serve as a leading point in identifying novel therapeutic agents that can redesign the tumour immune microenvironment by reducing infiltrating FOXP3-lymphocytes, and modifying their signalling pathways.
- Pathology, Oral
- Head and Neck Neoplasms
- IMMUNOHISTOCHEMISTRY
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Statistics from Altmetric.com
Data availability statement
All data relevant to the study are included in the article or uploaded as online supplemental information.
Footnotes
Handling editor Munita Bal.
Twitter @aanchalkakkar
AK and AT contributed equally.
Contributors AK and AT are responsible for conception, design and overall supervision of the study. Clinical data collection and analysis were performed by RT, AT and AS. Histopathological material preparation, immunohistochemistry and its assessment were performed by AK and DR, and results were analysed by AK, RT and RS. Statistical analysis was performed by RKM. Manuscript was drafted by RT, DR and RS. AK and AT critically revised the manuscript, are responsible for overall content, and accept full responsiblity for the work as the guarantors. All authors read and approved the final manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
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